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Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea

Tuberculosis and Respiratory Diseases 2018년 81권 3호 p.222 ~ 227
 ( Yun Yeo-Jun ) - Ewha Womans University Ewha Medical Research Institute

 ( Lee Jong-Seok ) - International Tuberculosis Research Center
 ( Yoo Je-Chul ) - Jeju National University College of Medicine Department of Microbiology and Immunology
 ( Cho Eun-Jin ) - International Tuberculosis Reserch Center
 ( Park Da-Hee ) - Jeju National University College of Medicine Department of Microbiology and Immunology
 ( Kook Yoon-Hoh ) - Seoul National University College of Medicine Department of Microbiology and Immunology
 ( Lee Keun-Hwa ) - Jeju National University College of Medicine Department of Microbiology and Immunology

Abstract

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea.

Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence.

Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L.

Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

키워드

Mycobacterium tuberculosis; Drug Resistance, Multiple; Beta' Subunit of RNA Polymerase; Mutation
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